He is a doctor. He is a cripple - and according to himself, God cannot be crippled. He is almost a drug addict. He is definitely a pain in the ass. He is insightful, so insightful to the extent that it becomes annoying, and seemlingly antisocial, cynical and hypocritical. In a nutshell, people hate when he's right, but have to live with it, literally, because him being right saves lives.
It just occured to me the other day that "House" is like,you know, "CSI: Hospital".